The induction in nondiabetic animals of abnormalities which resemble those of diabetics provides an opportunity to study the pathogenesis of individual complications free from the whole range of variables encountered in the disease. The American Diabetic Association, in a review of animal models appropriate for the study of complications of diabetes mellitus indicated that one nondiabetic model system, the "sucrose intoxication model", is particularly attractive. In this model, rats are reared on diets containing 65% sucrose for 6 months or longer. Associated with the duration of feeding are vascular abnormalities in the retina and kidney (vessel atrophy, aneurism, proteinurea) and changes in nerve tissue (edema, increased endoneurial fluid pressure, polyglucosan accumulation within axons). Of particular interest is the high incidence of capillary closure which appears to precede the clinical abnormalities associated with diabetic microangiopathy. Understanding the etiology of capillary closure is thought by some to be the key factor to understanding the progression of vascular abnormalities in the disease. The applicant has recently completed a long term experiment using this model system in order to more clearly define the components of the high sucrose diet involved in the induction of retinal vascular abnormalities. In rats provided the high sucrose diet as their sole food source for 10 months, the most frequently observed retinal vascular abnormality was an atrophy of capillaries with concomitant appearance of numerous acellular strands and collapsed vessels. Of particular importance was the observation that the vascular damage, including the capillary closure, could be prevented by supplementing the high sucrose diet with the essential elements Cr and Se and by raising the level of lipid in the diet. The purpose of this proposal is to determine in more detail the scope of the damage induced by the high sucrose diet, and the protection afforded by supplementation. The proposed research will establish if the damage to the retinal vasculature, in particular the development of collapsed atrophic capillaries, is accompanied by changes in the permeability of the vessels and a selective loss of cell types from the capillary walls. In addition, those factors in the supplementation which protected against the development of microangiopathy will be identified, and the degree of protection and relation to capillary leakage, cell loss and histopathological damage quantified.